Radiation Therapy and Fluorouracil With or Without Combination Chemotherapy Followed by Surgery in Treating Patients With Stage II or Stage III Rectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00335816
First received: June 8, 2006
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Fluorouracil may also make tumor cells more sensitive to radiation therapy. Leucovorin calcium may protect normal cells from the side effects of chemotherapy, and it may help fluorouracil work better by making tumor cells more sensitive to the drug. Giving radiation therapy together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with fluorouracil with or without combination therapy works in treating patients who are undergoing surgery for stage II or stage III rectal cancer.


Condition Intervention Phase
Colorectal Cancer
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Procedure: conventional surgery
Radiation: radiation therapy
Other: laboratory biomarker analysis
Genetic: DNA analysis
Genetic: polymerase chain reaction
Other: immunohistochemistry staining method
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Timing of Rectal Cancer Response to Chemoradiation

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Rate of pathologic complete response [ Time Frame: Determined at the time of surgery ] [ Designated as safety issue: No ]
  • Effect of different chemoradiation-to-surgery intervals on rate of pathologic complete response and surgical difficulty. [ Time Frame: Measured at the time of surgery ] [ Designated as safety issue: No ]
  • Effect of different chemoradiation-to-surgery intervals on postoperative complications [ Time Frame: 30 days after surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 248
Study Start Date: August 2008
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (Closed to Enrollment)
All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil intravenously continuously over 24 hours 7 days a week for 6 weeks. Patients undergo standard surgical resection after completion of chemoradiation therapy..
Drug: fluorouracil
Given IV
Procedure: conventional surgery
Patients undergo surgery
Radiation: radiation therapy
Patients undergo radiotherapy
Other: laboratory biomarker analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Experimental: Group 2 (Closed to Enrollment)
All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1-2. Treatment repeats every 14 days for 2 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Procedure: conventional surgery
Patients undergo surgery
Radiation: radiation therapy
Patients undergo radiotherapy
Other: laboratory biomarker analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Experimental: Group 3 (chemotherapy, FOLFOX, conventional surgery)
All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 4 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Procedure: conventional surgery
Patients undergo surgery
Radiation: radiation therapy
Patients undergo radiotherapy
Other: laboratory biomarker analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Experimental: Group 4 (chemotherapy, FOLFOX, conventional surgery)
All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 6 courses. After the last week of post- radiation chemotherapy, patients undergo standard surgical resection. Patients then receive 3 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Procedure: conventional surgery
Patients undergo surgery
Radiation: radiation therapy
Patients undergo radiotherapy
Other: laboratory biomarker analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry

Detailed Description:

OBJECTIVES:

I. To determine the rate of pathologic complete response to chemoradiation (no evidence of residual tumor in the resected specimen) of Stage II and Stage III rectal cancers that are staged preoperatively by endorectal ultrasound (ERUS) or magnetic resonance imaging (MRI), treated according to a standardized chemoradiation and surgery protocol, and evaluated by a systematic pathologic exam of the surgical specimen.

II. To study the effect of different chemoradiation-to-surgery intervals on the rate of pathologic complete response, on surgical difficulty, and on postoperative complications.

III. To investigate the feasibility of using sensitive molecular assays to detect tumor cells in the tumor bed and regional lymph nodes of rectal cancer specimens, with or without pathologic complete response to preoperative chemoradiation.

OUTLINE:

Patients are assigned to 1 of 4 treatment groups. All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil intravenously (IV) continuously over 24 hours 7 days a week for 6 weeks.

GROUP I (closed to enrollment): Patients undergo standard surgical resection after completion of chemoradiation therapy.

GROUP II (closed to enrollment): Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1-2. Treatment repeats every 14 days for 2 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

GROUP III: Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 4 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

GROUP IV: Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 6 courses. After the last week of post- radiation chemotherapy, patients undergo standard surgical resection.

In all groups, treatment continues in the absence of disease progression or unacceptable toxicity. A

fter completion of study treatment, patients are followed up for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have an Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1, or comparable Karnofsky performance status
  • Patients must have histologically confirmed invasive adenocarcinoma of the rectum Distal border of the tumor must be within 12 cm from the anal verge as measured on rigid proctoscopic exam
  • Patients must have Stage II (uT3-4, uN0) or Stage III (any T, uN1-2) tumors, as confirmed by ERUS or MRI; females with anterior tumors invading the posterior vaginal wall (uT4) and males with anterior tumors that invade the seminal vesicles or adjacent organs (uT4) will also be eligible provided they undergo an extended resection including the organs involved
  • Patients with high grade obstruction that impedes the ERUS exam are eligible for the study provided they can be staged by MRI
  • Patients with synchronous or metachronous colorectal cancer are eligible for the study on condition that they are treated for rectal cancer in accordance with the protocol
  • Patients with the following are NOT allowed on study:

    • Metastatic disease or other primaries
    • Locally recurrent rectal cancer
    • Previously documented history of Familial Adenomatous Polyposis
    • History of Inflammatory Bowel Disease
    • History of prior radiation treatments to pelvis
    • History of clinically significant cardiac disease (i.e., Class 3-4 congestive heart failure, symptomatic coronary artery disease, uncontrolled arrhythmia, and/or myocardial infarction within the previous 6 months
    • History of uncontrolled seizures or clinically significant central nervous system disorders
    • History of psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance
    • History of allergy and/or hypersensitivity to 5-fluorouracil (fluorouracil), leucovorin (leucovorin calcium), and/or oxaliplatin
    • History of difficulty or inability to take or absorb oral medications
  • Patients must have adequate bone marrow, hepatic and renal function within 7 days prior to registration
  • White blood cells (WBC) >= 3,000 mm^3
  • Absolute neutrophil count (ANC) > 1,500 mm^3
  • Hemoglobin > 9.5 mg/dl
  • Platelet count >= 100,000 mm^3
  • Total bilirubin =< 1.5 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.0 times institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.0 times ULN
  • Alkaline phosphatase =< 2.0 times ULN
  • Serum creatinine =< 1.5 times ULN
  • Patients with hereditary non-polyposis colorectal cancer are eligible for the study provided they meet the rest of the eligibility criteria
  • Patients who have experienced a prior malignancy should have received potentially curative therapy for that malignancy, and should be cancer-free for at least five years from the date of initial diagnosis (Exceptions: patients treated for basal cell carcinoma, or carcinoma in-situ of the cervix)
  • Patients of reproductive potential should agree to use an effective method of birth control when undergoing treatments with known or possible mutagenic or teratogenic effects; all female participants of childbearing potential must have a negative urine or serum pregnancy test within two weeks prior to study registration
  • Patients or the patient's legally acceptable representative must provide written authorization to allow the use and disclosure of protected health information; NOTE: this may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration or the initiation of any study-specific procedures
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00335816

Locations
United States, California
Cancer Care Center at John Muir Health - Concord Campus
Concord, California, United States, 94524-4110
City of Hope Medical Center
Duarte, California, United States, 91010-3000
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, United States, 92868
St. Joseph Hospital Regional Cancer Center - Orange
Orange, California, United States, 92868-3849
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Washington Cancer Institute at Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Colon and Rectal Surgery, Incorporated
Omaha, Nebraska, United States, 68114
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
United States, Vermont
Vermont Cancer Center at University of Vermont
Burlington, Vermont, United States, 05405-0110
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Julio Garcia-Aguilar, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00335816     History of Changes
Other Study ID Numbers: mskcc 12-201, P30CA033572, CHNMC-07182, UCSF-H44287-23127-03, UMN-2003UC036, UCSF-03451, CDR0000458059, R01CA090559
Study First Received: June 8, 2006
Last Updated: April 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on April 23, 2014